Tumor recognition following Vgamma9Vdelta2 T cell receptor interactions with a surface F1-ATPase-related structure and apolipoprotein A-I

Immunity. 2005 Jan;22(1):71-80. doi: 10.1016/j.immuni.2004.11.012.


Vgamma9Vdelta2 T lymphocytes, a major gammadelta T lymphocyte subset in humans, display cytolytic activity against various tumor cells upon recognition of yet uncharacterized structures. Here, we show that an entity related to the mitochondrial F1-ATPase is expressed on tumor cell surface and promotes tumor recognition by Vgamma9Vdelta2 T cells. When immobilized, purified F1-ATPase induces selective activation of this lymphocyte subset. The Vgamma9Vdelta2 T cell receptors (TCR) and the F1-ATPase also bind a delipidated form of apolipoprotein A-I (apo A-I), as demonstrated by surface plasmon resonance. Moreover, the presence of apo A-I in the culture medium is required for optimal activation of Vgamma9Vdelta2 T cells by tumors expressing F1-ATPase. This study thus describes an unanticipated tumor recognition mechanism by Vgamma9Vdelta2 lymphocytes and a possible link between gammadelta T cell immunity and lipid metabolism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apolipoprotein A-I / metabolism*
  • Humans
  • Immobilization
  • Jurkat Cells
  • Kinetics
  • Ligands
  • Lymphocyte Activation
  • Neoplasms / immunology*
  • Protein Binding
  • Proton-Translocating ATPases / metabolism*
  • Receptors, Antigen, T-Cell / metabolism*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Surface Plasmon Resonance
  • Surface Properties
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • Tumor Cells, Cultured


  • Apolipoprotein A-I
  • Ligands
  • Receptors, Antigen, T-Cell
  • Receptors, Antigen, T-Cell, gamma-delta
  • Proton-Translocating ATPases